Losartan as an ACE inhibitor: a description of the mechanism of action through quantum biochemistry

Losartan (LST) is a potent and selective angiotensin II (Ang II) type 1 (AT1) receptor antagonist widely used in the treatment of hypertension. The formation of Ang II is catalyzed by the angiotensin I-converting enzyme (ACE) through proteolytic cleavage of angiotensin I (Ang I), which is involved in the control of blood pressure. Despite the vast literature on the relationship of losartan with the renin-angiotensin system (RAS), the actions of losartan on the sACE enzyme are so far poorly understood. In view of this, we investigated how losartan can interact with the sACE enzyme to block its activity and intracellular signaling. After performing docking assays following quantum biochemistry calculations using losartan and sACE crystallographic data, we report that their interaction results reveal a new mechanism of action with important implications for understanding its effects on hypertension.

Automated summary

Losartan, a widely used hypertension medication, acts as a selective antagonist of angiotensin II receptor to reduce blood pressure. In this study, we investigated the interaction between losartan and sACE enzyme using molecular docking assays and quantum biochemistry calculations. Our findings reveal a new mechanism of action that has important implications for understanding the effects of losartan on hypertension.